Endocrine Abstracts

Dopamine receptor type 2 (DRD2) agonists (DA) are the first-choice treatment for prolactin (PRL)-secreting pituitary tumors, but poorly effective in non-functioning (NF)-PitNETs. Along with G protein-dependent signaling, DRD2 also mediates non-canonical beta-arrestin-dependent pathways, where reduction of AKT phosphorylation plays a leading role for the antiproliferative effect of DRD2 in pituitary tumors. Through UNC9994 and MLS1547, a beta-arrestin 2-biased and a G protein-b...

Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor of the parafollicular thyroid C cells. Although somatostatin (SS) receptors (SSTs) are expressed by MTCs, treatment with octreotide, specific for SST2, has shown poor efficacy in reducing MTC proliferation, whereas pasireotide, a multi-receptor SS analogue with preferential binding to SST5, has recently demonstrated antiproliferative effects in persistent postoperative MTCs. In vitro data in human MTC ce...

Somatic mutations in the ubiquitin specific peptidase 8 (USP8) gene have been associated with higher levels of somatostatin (SS) receptor subtype 5 (SSTR5) in adrenocorticotroph hormone (ACTH)-secreting pituitary neuroendocrine tumors (PitNETs). However, a correlation between the USP8 mutational status and favorable responses to pasireotide, the somatostatin multi-receptor ligand acting especially on SSTR5, has not been investigated yet. Here, we studied the impact of USP8 mut...

The mTOR inhibitor everolimus has been shown to display antimitotic effects on diverse neoplasms, including pituitary neuroendocrine tumors (PitNETs); however, its effect is reduced by an escape mechanism that increases AKT phosphorylation (P-AKT) leading to survival pathway activation. Dopamine receptor type 2 (DRD2) reduces p-AKT in some non-functioning PitNETs (NF-PitNETs) and in lactotrophs MMQ cells, through a α-arrestin 2-dependent mechanism. This study aim...

The majority of adrenocortical carcinomas (ACC) overexpress insulin-like growth factor 2 (IGF2). Although IGF2 drives a proliferative autocrine loop by binding to IGF1R and the isoform A of the insulin receptor (IRA), most studies focused on IGF1R. Recently, a high expression of IRA was observed in ACC vs normal adrenal tissues (NA), suggesting its potential involvement in modulating IGF2 effects in adrenocortical tumorigenesis. Aim of this study was to investigate the specifi...